Combined effects of glutathione S-transferase polymorphisms and thyroid cancer risk

Since exposure to ionizing radiation, a risk factor for thyroid cancer, may produce genotoxins potentially eliminated by glutathione-S-transferases, we conducted a case control study to evaluate the role of the GSTM1- and GSTT1-null genotypes and GSTP1 polymorphisms in thyroid cancer. The frequency of GSTP1 Ile/Ile, GSTM1-,and GSTT1-null genotypes was increased in cancer patients when compared with control population. Considering the genotypes over-represented in thyroid cancer patients as potential risk genotypes, we carried out an odds ratio (OR) analysis considering the presence of none, one, two, or three risk genotypes. The results obtained showed that the presence of three potentially risk alleles (GSTM1 null, GSTT1 null, and GSTP1 Ile/Ile) lead to a significant OR increase for all the cases, irrespective of the type of tumor (OR = 2.91), for papillary (OR = 3.64) but not for follicular tumors. The presence of GSTP1 Ile/Ile leads to a significant later age of tumor onset when compared with GSTP1 Ile/Val and Val/Val (P < 0.05), suggesting a possible association between GSTP1 Ile/Ile and the age of disease manifestation. These results suggest that combined GST polymorphisms lead to a moderate increased risk for thyroid cancer, especially for the papillary type, and GSTP1 polymorphisms might modulate the age of onset of the disease. (C) 2004 Elsevier Inc. All rights reserved.